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21.
《Bioorganic & medicinal chemistry letters》2017,27(22):5040-5045
A series of conformationally restricted benzopyran based triarylethylenes has been synthesized and characterized as potential growth inhibitors of breast carcinoma cells. The synthesized compounds (14a–b, 15a and 16a–e) presented significant growth inhibition of ER+ and ER− breast cancer cells within the range of IC50 0.55–9.96 µM. Amongst other, 16c showed potent anticancer activity at IC50 0.95 µM in MCF-7 cells with good selectivity (Selectivity Index 4.47) towards healthy cells. The mechanistic studies for 16c were performed to elucidate possible mode of action which showed 16c elicited anticancer activity through necroptosis process. 相似文献
22.
雌激素对淀粉样β蛋白代谢的调节和毒性缓解 总被引:2,自引:0,他引:2
以淀粉样β蛋白为主的老年斑胞外沉积和神经元内神经原纤维缠结,是阿尔采末病(AD)特征性的病理学改变。近来,人们逐渐认可淀粉样蛋白假说,即认为淀粉样蛋白沉积是AD最初起因。研究人员正在寻找针对淀粉样β蛋白沉积的药物,雌激素是其中之一。初步的工作证明,雌激素能够调节淀粉样β蛋白前体代谢,减少淀粉样β蛋白生成,也能够减轻淀粉样B蛋白引起的免疫炎症反应、氧应激对细胞造成的损伤,和对抗细胞凋亡。 相似文献
23.
Sex hormones have actions in brain regions important for emotion, including the amygdala and prefrontal cortex. Previous studies have shown that cyclic sex hormones and hormone therapy after menopause modify responses to emotional events. Thus, this study examined whether hormone therapy modified emotion-induced brain activity in older women. Functional magnetic resonance imaging (fMRI), behavioral ratings (valence and arousal), and recognition memory were used to assess responses to emotionally laden scenes in older women currently using hormone therapy (HT) and women not currently using hormone therapy (NONE). We hypothesized that hormones would affect the amount or persistence of emotion-induced brain activity in the amygdala and ventrolateral prefrontal cortex (VLPFC). However, hormone therapy did not affect brain activity with the exception that NONE women showed a modest increase over time in amygdala activity to positive scenes. Hormone therapy did not affect behavioral ratings or memory for emotional scenes. The results were similar when women were regrouped based on whether they had ever used hormone therapy versus had never used hormone therapy. These results suggest that hormone therapy does not modify emotion-induced brain activity, or its persistence, in older women. 相似文献
24.
目的:通过观察雌激素对子宫内膜癌KLE细胞中Notch信号通路的影响,探讨过表达雌激素核受体(estrogenreceptor,ER)是否可以恢复雌激素对Notch信号通路的调控作用,继而调节细胞增殖活性。方法:MTT检测雌激素及Notch信号通路对细胞增殖活性的影响;RT.PCR及Westem.blotting检测雌激素及Notch通路抑制剂DAPT对Notch表达的影响;质粒的抽提及转染使KLE细胞中的雌激素核受体ER过表达。结果:雌激素呈剂量依赖效应促进KLE细胞的增殖活性,其中以雌激素浓度为1.0×10-9M时最明显(相对于对照组为1.25±0.026,P〈0.05);抑制Notch信号通路的表达可以明显下调KLE细胞的增殖活性(0.76±0.02,P〈0.05);在KLE细胞中,雌激素对Notch的表达没有明显的调控作用,但是将其雌激素核受体过表达后,雌激素可明显上调Notch的表达,并显著促进细胞的增殖活性(1.24±0.02,P〈0.05)。结论:在ER阴性的子宫内膜癌细胞中过表达ER,可以恢复雌激素对Notch信号通路的调控,从而进一步的调控细胞增殖活性。 相似文献
25.
Horjales S Cota G Señorale-Pose M Rovira C Román E Artagaveytia N Ehrlich R Marín M 《Archives of biochemistry and biophysics》2007,467(2):139-143
As an approach to understand how translation may affect protein folding, we analyzed structural and functional properties of the human estrogen receptor alpha synthesized by different eukaryotic translation systems. A minimum of three conformations of the receptor were detected using limited proteolysis and a sterol ligand-binding assay. The receptor in vitro translated in rabbit reticulocyte lysate was rapidly degraded by protease, produced major bands of about 34 kDa and showed a high affinity for estradiol. In a wheat germ translation system, the receptor was more slowly digested. Two soluble co-existing conformations were evident by different degradation patterns and estradiol binding. Our data show that differences in the translation machinery may result in alternative conformations of the receptor with distinct sterol binding properties. These studies suggest that components of the cellular translation machinery itself might influence the protein folding pathways and the relative abundance of different receptor conformers. 相似文献
26.
Cytotechnology - Bone mass is regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Osteoporosis is a bone metabolism disorder in which bone mass decreases due to... 相似文献
27.
本文对采用细胞化学法测定乳腺癌内雌激素受体[ER]所用的荧光配体17-FE是否也是与ER上结合位点相结合的问题进行了探讨。在测定17-FE对[~3H]E_2与兔子宫上清液内ER结合的影响后,指出:17-FE对[~3H]E_2与ER的结合具有抑制作用,且其抑制作用随着17-FE浓度的提高而加大。在一系列不同浓度[~3H]E_2下测定其与ER的特异结合,同时测定加入不同浓度17-FE后的特异结合量,以Lineweaver-Burk和Scate-bard法分别作图。分析结果均显示为竞争性抑制曲线,可见17-FE和[~3H]E_2一样是与兔子宫上清液内ER上的结合位点相结合的。因此采用细胞化学法测定ER时,17-FE是一理想的配体。 相似文献
28.
An individual's position in a social hierarchy profoundly affects behavior and physiology through interactions with community members, yet little is known about how the brain contributes to status differences between and within the social states or sexes. We aimed to determine sex-specific attributes of social status by comparing circulating sex steroid hormones and neural gene expression of sex steroid receptors in dominant and subordinate male and female Astatotilapia burtoni, a highly social African cichlid fish. We found that testosterone and 17β-estradiol levels are higher in males regardless of status and dominant individuals regardless of sex. Progesterone was found to be higher in dominant individuals regardless of sex. Based on pharmacological manipulations in males and females, progesterone appears to be a common mechanism for promoting courtship in dominant individuals. We also examined expression of androgen receptors, estrogen receptor α, and the progesterone receptor in five brain regions that are important for social behavior. Most of the differences in brain sex steroid receptor expression were due to sex rather than status. Our results suggest that the parvocellular preoptic area is a core region for mediating sex differences through androgen and estrogen receptor expression, whereas the progesterone receptor may mediate sex and status behaviors in the putative homologs of the nucleus accumbens and ventromedial hypothalamus. Overall our results suggest sex differences and similarities in the regulation of social dominance by gonadal hormones and their receptors in the brain. 相似文献
29.
30.
Modulation of osteoclastogenesis in porcine bone marrow cultures by quercetin and rutin 总被引:3,自引:0,他引:3
Rassi CM Lieberherr M Chaumaz G Pointillart A Cournot G 《Cell and tissue research》2005,319(3):383-393
Flavonols, in contrast to soybean isoflavones, are the most abundant phytoestrogens in western diets, being present in onions, beans, fruits, red wine, and tea. They may protect against atherosclerosis, inhibit certain cancer cell types, and reduce bone resorption. The most widely distributed flavonol is quercetin, which occurs mainly as its glycoside, rutin, but data are very scarce regarding the precise mechanism of action of these compounds on bone-resorbing cells at concentrations similar to those detected in human plasma. We have therefore investigated the effects of nanomolar concentrations of quercetin and rutin on the development and activity of osteoclasts in vitro compared with the effects of 17-estradiol. Nonadherent porcine bone marrow cells were cultured on dentine slices in the presence of 10 nM 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), with or without 10 nM quercetin, 10 nM rutin or 10 nM 17-estradiol for 11 days. Multinuclear TRAP+ cells that resorbed dentine (osteoclasts) developed in the presence of 1,25(OH)2D3, but their number was significantly reduced by quercetin, rutin, and 17-estradiol (P < 0.05). Like 17-estradiol, both flavonols also significantly reduced resorption (P<0.05) as assessed by the size of pits resorbed on dentine slices. Osteoclasts and osteoclast progenitors contained estrogen receptor (ER), ER, and RANK proteins. Both flavonols increased nuclear ER protein and decreased ER protein of osteoclast progenitors. Moreover, rutin reduced RANK protein, whereas 17-oestradiol and quercetin promoted apoptosis by cleavage of caspase-8 and caspase-3. All the effects of flavonols were reversed by 1 M ICI 182,780, an estrogen antagonist. Thus, the anti-resorbing properties of flavonols are mainly mediated by ER proteins through the inhibition of RANK protein or the activation of caspases.C.M.R. was supported by a grant from CAPES (Department of Education, Brasilia, Brasil). 相似文献